title: Innate and adaptive immune activation in the brain of MPS IIIB mouse model.
abstract: Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to alpha-N-acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real-time quantitative reverse transcriptase-polymerase chain reaction, we demonstrated significant up-regulation of numerous immune-related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll-like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect.
authors.affiliation: Center for Gene Therapy, Columbus, Ohio 43205, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: DiRosario
authors.forename: Erin
authors.initials: E
authors.lastname: Divers
authors.forename: Chuansong
authors.initials: C
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Etter
authors.forename: Alyssa
authors.initials: A
authors.lastname: Charrier
authors.forename: Peter
authors.initials: P
authors.lastname: Jukkola
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.forename: Victoria
authors.initials: V
authors.lastname: Best
authors.forename: David L
authors.initials: DL
authors.lastname: Newsom
authors.forename: Douglas M
authors.initials: DM
authors.lastname: McCarty
authors.forename: Haiyan
authors.initials: H
authors.lastname: Fu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001323:Autoantibodies; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008198:Lymph Nodes / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009084:Mucopolysaccharidosis III / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D011239:Prednisolone / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology / Q000503:physiopathology
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; D011239:Prednisolone